SARS-CoV-2 and Respiratory Syncytial Virus Coinfection in Hospitalized Pediatric Patients

Abstract

In this study, children under 24 months of age hospitalized with respiratory compromise due to COVID-19 were retrospectively analyzed according to the event of coinfection with respiratory syncytial virus. Of 32 patients, 18.7% had coinfection and these had a significantly longer length of stay. There were no differences regarding need for intensive care, mechanical ventilation or mortality rates.

The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new virus identified in late 2019 in China,¹ spread throughout the world in 2020 leaving, by December 11, a total of 68,845,368 cases and 1,570,304 deaths.² It presents with mainly respiratory symptoms, but other manifestations may occur.^3–5 Studies have shown that the pediatric population is less affected by this new virus, representing 1%–5% of total cases. Children also tend to have milder symptoms, better prognosis and lower mortality rates than adults.^3–5

Respiratory syncytial virus (RSV) is the predominant virus involved in bronchiolitis, one of the most important respiratory infections in children under 24 months of age, responsible for 199,000 deaths a year, mainly in developing countries.⁶

There are only a few studies that assess SARS-CoV-2 viral coinfection in children, and there is no consensus yet on how it might affect clinical course or outcome.

The main objective of this study was to describe and compare clinical characteristics and outcomes of pediatric patients under 24 months of age hospitalized with acute respiratory compromise due to COVID-19 with and without RSV coinfection.

MATERIAL AND METHODS

This was an observation retrospective study carried out in a public secondary care children’s hospital in the city of Guarulhos, the second most populous city in the state of São Paulo, Brazil.

Acute respiratory compromise was defined, according to the Brazilian Health Ministry, as fever associated with respiratory symptoms plus respiratory discomfort, such as tachypnea or dyspnea, or hypoxemia.

Inclusion criteria were as follows: children under 24 months of age hospitalized from March 1 to September 30, 2020 with acute respiratory compromise caused by COVID-19 and who had also been tested for RSV.

RSV testing is routinely performed in our hospital for children under 24 months of age hospitalized with respiratory symptoms.

Nasopharyngeal secretion samples were obtained from patients at hospitalization time and sent to the laboratory for analysis. Detection methods included RT-PCR for SARS-CoV-2 and chemiluminescence for RSV. When hospitalization occurred before the third day of the onset of symptoms, another sample was collected between the third and seventh days, especially for SARS-CoV-2 testing.

It is known that RSV has a characteristic seasonality so, for the purpose of analyzing whether RSV infection happened more frequently in a specific time frame, cases were divided into 2 time periods according to the date of the diagnosis of acute respiratory compromise (first from March 1 to June 15—which encompasses the typical RSV seasonality in our geographic region—and second from June 16 to September 30) for comparison.

Statistical analysis was performed with Prism 9 software. Numerical variables were all of nonnormal distribution and thus, described as median and compared with Mann–Whitney U test. Categorical variables were described as percentage and compared with the Fisher exact test. Statistical significance was set at P < 0.05.

The study was approved by the Ethics in Human Research Committee of the University of Guarulhos.

RESULTS

During the studied period, 32 patients fulfilled the inclusion criteria. Of those, 6 had both RSV and SARS-CoV-2 detected, resulting in a viral coinfection rate of 18.7%. All but one case was community acquired. The only nosocomial case was that of a 2-month-old child with congenital heart disease who acquired both RSV and SARS-CoV-2 after about 1 month of hospitalization in the pediatric intensive care unit, during an RSV outbreak.

Twenty-one cases happened in the first time period (5 of which had viral coinfection) and 11 in the second time period (only 1 presenting with viral coinfection). After statistical analysis, there was no significant difference in the risk for RSV infection in any of the time periods (P = 0.63).

Table 1 shows the characteristics and outcomes of patients with and without viral coinfection. There was no significant difference in sex, age or the presence of underlying medical condition between the 2 groups. In the “other” category of underlying medical conditions in the group without RSV coinfection, we found 1 patient with prematurity, 1 with a genetic syndrome and 1 with respiratory atopic disease.

TABLE 1. - Characteristics and Outcomes of Patients With and Without Viral RSV/SARS-CoV-2 Coinfection

	With RSV Coinfection	Without RSV Coinfection	P
N	6	26	—
Male sex (%)	33.3%	65.3%	0.19
Age (median, mo)	6	3	0.94
Underlying medical conditions (%)	50%	23%	0.31
Chronic pulmonary disease (%)	33.3%	7.7%	0.15
Congenital heart disease (%)	16.7%	3.8%	0.34
Other (%)	0%	11.5%	>0.99
Fever (%)	83.3%	61.4%	0.63
Gastrointestinal symptoms (%)	0%	26.9%	0.29
Intensive care (%)	16.6%	7.6%	0.47
Mechanical ventilation (%)	16.6%	3.8%	0.34
Length of stay (median, days)	7	3	0.0003
Mortality rate (%)	0%	3.8%	>0.99

Despite statistical nonsignificance, it is worth to say that there were no patients in the coinfection group with associated gastrointestinal symptoms, whereas 26.9% of patients in the group without coinfection presented with these manifestations.

Regarding clinical course, patients with coinfection had a longer length of stay (7 vs. 3 days) but there was no difference in the need for intensive care or mechanical ventilation.

There were no differences in the mortality rates between the 2 groups. Only 1 child died during the studied period, a 2-month-old premature girl with bronchopulmonary dysplasia who did not have viral coinfection

There were no patients with viral-bacterial coinfection at the time of acute respiratory compromise diagnosis.

DISCUSSION

This was a single-center observational retrospective study aimed at describing and comparing viral SARS-CoV-2/RSV coinfection in children under 24 months of age hospitalized with acute respiratory compromise.

There is not much data on SARS-CoV-2 viral coinfection, especially in children. One study in the United States found that only 2% of SARS-CoV-2 infections in children had also another viral identification.⁷ Another study in China revealed that 51.4% of COVID-19 pediatric cases had coinfection with another common respiratory pathogen, but most cases (57.8%) involved Mycoplasma pneumoniae and only 15.7% involved other respiratory viruses (RSV and influenza).⁸ In our study, there was 18.7% of coinfection with RSV in children under 24 months of age hospitalized with acute respiratory compromise due to COVID-19 and, in these cases, patients had longer length of stay than those without coinfection.

This study involved only 7 months of the year and thus, it is insufficient to add much knowledge to the seasonal behavior of RSV pediatric infections in this very atypical year of 2020, but, superficially, it showed that RSV circulated throughout the studied period and there was no higher risk for viral coinfection in the regular RSV peak circulation month (April) in our region.⁹

Despite shining a light on viral SARS-CoV-2 coinfection, this is a small single-center study and larger studies still need to be conducted regarding its impact in the clinical course and outcomes of pediatric patients.